What are antiplatelet drugs and how do they work?
There are numerous anti-platelet agents available. The most common is aspirin which is an anti-platelet and anti-pyretic agent which works by irreversibly inhibiting cyclooxygenase (responsible for producing prostaglandins and thromboxane), which in turn reduces thromboxane A2 production. This is required since thromboxane is involved in stimulating new platelets, as well as allowing them to bind together via the GP IIb/IIIa complex in the platelet membrane via fibrinogen which builds upon the blood clots. Maximum platelet inhibition is achieved at 32-75 mg. Any higher than this results in GI side effects such as bleeding, and also hypersensitivity. This bleeding is due to thromboxane being a prostaglandin which would normally otherwise protect against acid erosion. It is now only used in CVD due to the benefit/risk ratio. In those with CVD and on aspirin, it is not uncommon for these patients to also be on a proton pump inhibitor such as omeprazole.
It is commonly used due to it being cheap, and also used in secondary stroke prevention. Also, it is not given to children since it may cause Reye’s syndrome. Dipyridamole is also an antiplatelet drug. It prevents the uptake of adenosine, as well as inhibiting platelet phosphodiesterase (which causes the accumulation of cAMP and cGMP). It will also prevent the formation of thromboxane A2. Its only proven use is in stroke to prevent mortality when used with aspirin. It is given twice daily. However, 4/10 stop it due to severe headaches, flushing and GI upset. A newer anti-platelet agent is Ticlopidine, however, this caused a severe reduction in the number of platelets produced as well as agranulocytosis.
Clopidogrel is another antiplatelet which works by inhibiting the action of platelets by blocking ADP receptors on the platelets and thereby inhibiting their action (clot formation). It also impairs activation via the GPIIb/IIIa. It doesn’t cause GI irritation, although it can still cause bleeding in those susceptible to bleeding, or those with previous ulcers.
Aspirin+Clopidogrel will be given in the first few months after an MI, however, it is not given in combination for stroke patients since it can result in an increase in bleeding. It can also be used in those that can’t tolerate warfarin (WOSIS trial), and it is more expensive than aspirin. Finally, it is possible to give GPIIb/IIIa receptor antagonists which are given via IV immediately after a stent as it will prevent stenosis of a metal stent and rethrombosis in normal stents.